The twenty first century has witnessed an explosion of molecular biology techniques, amazing advances in imaging, and the design of unique imaging probes. Despite the tremendous strides made in these areas of science, the cure for cancer remains beyond our grasp. Cancer is a complex disease and the apparent impenetrability of the disease is largely due to the multiple, often redundant pathways, which appear to evolve through the genetic instability of cancer cells. The ability to identify and image key common pathways specific to cancer cells, and the ability to image the effectiveness and outcome of strategies designed against these targets is critically important in the treatment of this disease. The vision of our JHU ICMIC is to combine state-of-the-art imaging capabilities with powerful molecular biology techniques to define strategies with 'intent to cure'. In this proposal we have drawn upon our human resources at JHU to create a center consisting of a multidisciplinary group of premier individuals with diverse skills focused on translating molecular capabilities into imaging possibilities with the single purpose of understanding and curing cancer. Nearly all of the investigators participating in this ICMIC have interactive collaborative projects with one or more of the other investigators. The synergism generated by the collective skills of this unique group of individuals will lead to significant advances in the understanding of cancer and its treatment. The existing P20 program as well as the SAIRP have laid a strong foundation for the establishment of a world class in vivo cellular molecular imaging program at Johns Hopkins. The current proposal builds upon this strong foundation. Our JHU ICMIC structure consists of four interactive and closely related research components focused on hypoxia, HIF-1, and exploiting the hypoxia response element to target cancer cells through choline kinase inhibition. These research components are anchored by the participation of world renowned expertise in HIF-1. The research components will utilize MR, PET and Optical imaging technology to understand cancer vascularization, invasion and metastasis, to achieve effective cancer therapy. We have selected five developmental projects which are highly relevant to the goals of the ICMIC and interactive with the research components. Five resources devoted to adminstration, molecular biology, imaging, probes, and translational application will provide the infrastructure to support the research activities of the ICMIC. A career developmental program will train the future champions of molecular imaging in cancer. An advisory board consisting of the best scientists at Hopkins, and at several institutions in the US and abroad, will provide critical evaluation of the progress made. Strong institutional support and the advocacy of the Dean, Vice-Dean and Chairs of Radiology, Oncology and Biomedical Engineering will further ensure the success of the JHU ICMIC and fulfillment of its vision.